Research Strategy

Our research strategy includes overall principles and criteria to guide prioritisation of the research focus and identify specific areas of priority.


Visit here for details on 2018 CBS deficiency Research Grants.

Our Research Strategy aims to:

  • Define key priorities for future research for Classical Homocystinuria (CBS deficiency); and
  • Guide prioritisation and evaluation of research grants funded by HCU Patient Community Groups.

Key Focus Areas

Several areas of unmet need in the diagnosis and management of Classical Homocystinuria have been identified through advice from academic researchers and clinical experts.  We have defined 3 key priority focus areas for future research and patient advocacy:

We expect our near-term Research Strategy to focus primarily on advancement of new treatment modalities, in order to maximize the benefit to patients and lesson the burden of strict dietary control.  We will use 3 guiding criteria for prioritisation and evaluation of research grants:

  • Potential risk/benefit of approach to improve patient care.
  • Probability research in this area would move forward without funding by HCU Network Australia and HCU Network America (HCUNAs).  Lower priority placed on an area if industry funding available.
  • Probability funding a project in this area would contribute significantly to progressing research in this area, including potentially attaining proof of concept to motivate industry funding.


HCU Network Australia and HCU Network America have agreed to collaborate in specific areas that can benefit from global perspective and coordination.  One such area is to promote research for Classical Homocystinuria, which is supported by a global Scientific Advisory Board.  Over time, we hope to include patient groups from other countries and to be able to expand focus beyond classical homocystinuria to include cobalamin deficiencies and methylation disorders that also cause elevated homocysteine levels.

Therapeutic Avenues

The current therapeutic objective is described in the Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. Click here to view the Guidelines.

There are several approaches being investigated for the treatment of classical homocystinuria. See our Investigational Therapies Research Map.

Enzyme Replacement Therapy (ERT) – Replace CBS enzyme

Enzyme Replacement Therapy (ERT)

What is it?

Enzyme replacement therapy (ERT) is a medical treatment, which replaces an enzyme in a patient where the enzyme is defective due to a genetic defect.  The product currently in development for classical homocystinuria is a synthetic version of the enzyme and is expected to be administered by a subcutaneous injection.

The safety and effectiveness of ERT has been shown in the treatment of some lysosomal storage diseases including Gaucher disease type I, Fabry disease, MPS I (Hurler syndrome), MPS II, MPS VI and Pompe.  ERT does not correct the underlying genetic defect and is not a curative approach but rather requires lifelong administration.

Gene Therapy – Deliver DNA to enable body to produce CBS enzyme

Gene Therapy

What is it?

Gene therapy is a treatment approach that involves delivering genetic material (DNA) into a person’s cells to compensate for defective genes.  The process involves using a vector (e.g. the adenovirus or common cold vector which is inactivated and has no biologic activity) to deliver the genetic material into the body.  The cells in the body (in the case of classical HCU, the liver cells) will then transcribe the DNA and produce the enzyme.  It is unknown how long the product will last and whether readministration will need to occur over time.

Alternative Enzymes– Use alternative enzymes to degrade

Methionine (Met) or Homocysteine (Hcy)

What is it?

There are other synthetic enzymes in development that are designed to degrade methionine (so that it is not converted to homocysteine) or directly degrade homocysteine.  These are expected to require infusions, most likely on a monthly basis.

CBS Protein Activation:  Administer small molecules to restore faulty

CBS enzyme function or activation

What is it?

Small molecules can be chemically synthesized and often taken in tablet or capsule form, in contrast to enzymes or other “biologics”, which are made via living organisms and  too “large” to be taken in tablet or capsule form so require injection or infusion.  There are a few small molecules being researched for HCU that would either activate the function of the CBS enzyme (which is a protein) or prevent its degradation, thereby increasing its effectiveness in lowering homocysteine levels.

Metabolic Pathway Modification:

Use nutrition or dietary supplements to address metabolic imbalance caused by HCU

What is it?

There are other approaches to modify the metabolic pathway through modulating sulphur containing amino acids through diet and/or supplements, but this approach needs to be validated in clinical trials to demonstrate any advantages over the current approach of protein restriction and supplementation with non-methionine amino acids.


What is it?

Formate is a substance made naturally at low levels within the cell from the breakdown of a range of amino acids, fatty acids and as an intermediate of sterol metabolism.  Research has shown that administration of sodium formate can reduce levels of homocysteine in mice, and especially when combined with betaine.  A new study in mice is being conducted by Ken Maclean, Ph.D., at University of Colorado, with a grant from HCU Network America and HCU Network Australia, to determine whether formate treatment combined with betaine could dramatically improve clinical outcome in HCU and conceivably remove the need for a methionine restricted diet.  Dr. Maclean will also utilise funding from the William R. Hummel Homocystinuria Research Fund to supplement this grant.


What is it?

Taurine is an naturally occurring sulfinic acid that acts to increase tissue levels of the major cellular antioxidant glutathione by exerting a cysteine sparing effect. In an animal model of HCU, the co-administration of taurine acted to normalize blood-clotting parameters, decrease inflammation in the vasculature and increased the effectiveness of the betaine response. In a recent short-term human pilot trial, taurine reversed endothelial dysfunction in human subjects with HCU.  Further studies of taurine are being considered.

Here is a schematic overview showing the biochemical cascade and how emerging therapeutic interventions address the biochemical or disease process.

Current Research Avenues

Classical homocystinuria was first reported by American physician D. A. Carson in 1962 followed by H. Mudd describing the enzyme defect in 1964.  Since his discovery much research has gone into both understanding the disease and investigating approaches for effective therapeutic treatments.

The HCU Networks sought to identify the therapeutic approaches under investigation for classical homocystinuria and characterise clinical and preclinical stage technologies in development.  The Investigational Therapies Research Map aims to summarise the treatment approaches being studied by academia and industry covering pre-clinical and clinical stage technologies.

The Research Map was developed based on information available in the public domain and provided by academic and industry researchers.  Interviews with leading researchers and clinicians served to expand and validate the Research Map and to provide expert input on the Research Strategy.

Expert input included:

  • Viktor Kozich – Project Advisor
  • Kimberley Chapman
  • Bart deGeest
  • Henk Blom
  • Jan Kraus
  • Warren Kruger
  • Andrew Morris
  • Bridget Wilcken
  • Ken Maclean
  • Johan Van Hove/Cynthia Frehauf*

Industry input included:

  • Aeglea Biotech*
  • Erytech*
  • Orphan Technologies*

*Provided input on specific program

Investigational Therapies Research Map

Our Research Map focuses on one of our key priorities:  Advance New Treatment Modalities.  The Research Map is not intended to be an exhaustive list of research activities around the world and does not include analysis on existing and emerging tools for diagnosis and disease monitoring.  Click here to view our Investigational Therapies Research Map

For a description on the different types of investigational therapies for Classical Homocystinuria please see Therapeutic Avenues.

To read about strengths and weaknesses of each approach view the Global Research Map: CBS deficient homocystinuria presentation by Margie McGlynn, President HCU Network America.  Note: the evaluation of each program is based on a compilation of input from expert interviewees and does not represent a consensus.

Scientific Advisory Board

A Scientific Advisory Board has been convened to advise the HCU Networks on key priorities and guide which specific projects should be funded.

The current members of the Scientific Advisory Board Include:

Professor Viktor Kožich, (Chair of SAB); MD, PhD, Professor of Medical Genetics and Head of Institute of Inherited Metabolic Disorders, General University Hospital in Prague and Charles University-First Faculty of Medicine, Prague, Czech Republic. Read Professor Kožich’s bio
Professor Bridget Wilcken AM, MD, FRACP, FRCPA (hon), FHGSA, emeritus consultant at the Children’s Hospital, Westmead, Sydney; part-time metabolic physician, Sydney Children’s Hospital, Australia. Read Professor Wilcken’s bio
Professor Matthias R. Baumgartner, Prof. Dr. med., Head of Division for Metabolic Diseases and Medical Director of the Swiss Newborn Screening Program, Kinderspital, Zürich, Switzerland. Read Professor Baumgartner’s bio
Professor Henk Blom, PhD, Head of laboratory for Clinical Biochemistry and Metabolism, Department of General Pediatrics, Canter for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany. Read Professor Blom’s bio
Professor Jan Kraus, Ph. D, Professor Pediatrics / Cell and Developmental Biology, University at Colorado U.S. Read Professor Kraus’ bio
Professor Warren Kruger, Ph. D, Full professor, Cancer Biology program at Fox Chase Cancer Center, Philadelphia, PA, U.S. Read Professor Kruger’s bio
Dr Andrew Morris, MD, Consultant and Senior Lecturer in Paediatric Metabolic Medicine. Willink Metabolic Unit, Central Manchester University Hospital, UK. Read Dr Morris’ bio
Dr Kimberly Chapman, MD, Ph.D., attending physician in Genetics and Metabolism, Children’s National: Assistant Professor of Pediatrics and Integrated Systems Biology, George Washington University, U.S. Read Dr Chapman’s bio

Patient Representatives:

Tara Morrison, BA LLB, Director & Chair, HCU Network Australia
Margaret McGlynn, R. Ph., Ph. D. (hon), President of Board, HCU Network America

Responsibilities of the Scientific Advisory Board

The responsibilities of the Scientific Advisory Board include:

  • Work with HCU Network Australia and HCU Network America (HCUNAs) (and other patient groups interested in funding grants) to develop research strategy and identify key priorities for funding.
  • Provide non-binding but informed guidance on matters specific to HCUNAs research and funding strategies, including opportunities for new programs or clinical trials.
  • Provide peer review for applications submitted to HCUNAs for funding and provide recommendations on specific projects to be funded.
  • Support any grant applications submitted by HCUNAs to other funding bodies.
  • Participate in periodic reviews of HCUNAs Research Strategy.

Download a copy of the Scientific Advisory Board’s Terms of Reference.

HCU Network Australia and HCU Network America are currently calling for Expressions of Interest (EOI) for:

  • Research Grants which provide funding for technologies to improve newborn screening (and potentially also aid in ongoing monitoring or screening of undiagnosed older individuals); and
  • Research Grants which provide funding for potential new therapies to treat homocystinuria caused by cystathionine beta synthase deficiency (with the ability to treat elevated homocysteine caused by methylation disorders and cobalamin deficiencies an added benefit).

Research Grants support innovative seed or pilot projects to produce preliminary data that would facilitate more substantial funding from federal agencies, foundations or corporations.  Research Grant awards are up to AUD $40,000 (HCU Network Australia) and/or US $50,000 (HCU Network America).  All applications submitted will be considered for funding by both organizations, though it is unlikely the same application would receive funding by both.

Important Dates:

  • EOI deadline for the submission: 15 January 2018
  • Notification of successful EOI: 1 March 2018  
  • Deadline for full applications: 1 May 2018
  • Funding decisions will be made in June 2018

How to apply for a Research grant:

Download full Expression of Interest instructions here.

EOIs will be reviewed by the Scientific Advisory Board, in consultation with HCU Network Australia and HCU Network America, and applicants will be notified by March 1, 2018 if they are invited to submit a full application.

Full applications will be due by May 1, 2018, and will subsequently be reviewed by our Scientific Advisory Board.  HCU Network Australia and HCU Network America Board of Directors will make the final funding decision on each grant application taking into consideration the advice of the Scientific Advisory Board and direct donor input.

For more information, please email: Tara Morrison at and Margie McGlynn at

Apply today for the HCU Travel Fellowship 2018


Application Guidelines / Terms and Conditions

HCU Network Australia welcome applications for its 2018 research and education travel fellowships. These grants are intended to foster professional development and continued learning opportunities for scientists and/or health professionals to improve the health and wellbeing of children and adults with Homocystinuria (HCU).

The principal aim is to encourage education, research and professional development for those interested in obtaining further HCU education or presenting relevant work at national or international conferences. Nurses, scientists, clinicians and other health care professionals working in either a clinical or research environment in Australia are eligible to apply.

Applications will be called for once per year, with up to $3,000 available.  The maximum amount that will be awarded to an individual for travel in Australia or New Zealand will be $750 and the maximum for travel to other overseas locations will be $3,000. The Fellowship(s) awarded are at the sole discretion of HCU Network Australia’s Executive Committee.

Deadline for submission of applications

Travel Fellowship 2018: 31st January 2018 for travel in the following 12 months.

The applications must meet the criteria described below. They will be reviewed by HCU Network Australia’s Executive Committee, whose decision will be final. No further discussion with the applicants will take place. It is expected that decisions on the fellowships will be made within four weeks of applications closing.

The Fellowship may be used for costs of flights, accommodation, or meeting registration. It will be paid in a single installment following receipt of proof in the form of receipts or directly to suppliers at the discretion of the approving group. Applicants are expected to purchase economy class airfares and choose cheaper accommodation options if appropriate. Anticipated expenditure on individual items must be clearly specified in the application.

We understand that these Fellowships may not cover the entire costs of the travel and we encourage applicants to supplement them by applying to other funding bodies, seeking conference travel grants, utilizing professional development allowances or other personal funding.


The following guidelines should be considered before submitting the application:

  • The conference/meeting/workshop for which grants are sought must have a substantial HCU component.
  • Applicants attending conferences, meetings or workshops for the purpose of educational development or training must clearly explain in the application how this event will help them develop professional skills required for their care of HCU patients or help them in their work aimed at helping those living with HCU.
  • Applicants attending conferences for purpose of presenting research or clinical findings need to submit proof of abstract acceptance for oral or poster presentation and must be the presenting author. Any presentation given needs to acknowledge funding support from HCU Network Australia.
  • Applicants should be willing to present at HCU Network Australia-sponsored events and share the knowledge they have gained with other health care professionals and the HCU community.
  • Applicants must provide a 2 page lay language report about the conference/training for the HCU Network Australia newsletter/website/media promotion within 1 month of returning.


Applications must consist of:

A CV no longer than 4 pages that must include the following details:

  • Name of applicant
  • Current position (i.e. clinician, nurse, researcher)
  • Institution
  • Supervisor
  • Education background (highest previous qualification/date of award/institution and current degree being pursued if applicable)
  • List of publications or clinical experience relating to working with HCU
  • Previous grants and awards if available


A covering letter from the applicant which includes:

  • Proposed dates, the cost of travel, accommodation and/or registration and a statement regarding relevant financial reasons for requesting meeting travel support.
  • Information about any other approved or outstanding applications to other funding bodies for the same travel.
  • For a conference: A description of the conference, a copy of any submitted abstract, and a personal statement highlighting how the applicant’s research/development would be enhanced by attending the conference.
  • For education/training activities: A description of the topics that will be covered during the meeting, how they relate to HCU, why is it important for the applicant to attend and how those topics would benefit the professional development of the individual and future care of patients with HCU.
  • A description of how the applicant proposes to share the knowledge that will be gained with other health care professionals and the HCU community.


A brief letter of support from the applicant’s supervisor addressing the above guidelines and a statement of eligibility. Any funding towards travel obtained from the applicant’s department/supervisor/institution should be confirmed in the letter of support.

Submission details

Applications should be sent to: The President, HCU Network Australia, PO Box 7484 BAULKHAM HILLS NSW 2153 or emailed to:

We would like to acknowledge DEBRA for their generosity in allowing HCU Network Australia to adopt their Travel Fellowship Terms and Conditions.
You can read more about DEBRA at