Our research strategy includes overall principles and criteria to guide prioritisation of the research focus and identify specific areas of priority.
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.
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
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 imbalances 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.
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
- Johan Van Hove/Cynthia Frehauf*
Industry input included:
- Aeglea Biotech*
- 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 und 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|
|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 (perhaps also have in blue bars to match other pages):
- 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.
The first meeting of the Scientific Advisory Board (SAB) for CBS deficiency was held on September 5, 2017. Based on the discussion at the meeting, a specific call for proposals is being developed to enable researchers to submit an expression of interest for submitting a full application for specific projects. The SAB will then determine which projects best meet the criteria and key priorities, and will request the researchers to submit a full application. The SAB will review the applications and advise the HCU Networks on which projects they recommend for funding. The HCU Networks will then make final decisions on what grants to provide based on the availability of funding.
The key priorities that will be included in the upcoming call for proposals include:
- Technologies or approaches to improve Newborn Screening
- New therapeutic approaches to classical homocystinuria
HCU Network Australia and HCU Network America would welcome discussions with any other patient groups or families affected by HCU who would be interested in providing financial support to enable more projects to be funded.
Apply today for the HCU Travel Fellowship 2016
Application Guidelines / Terms and Conditions
HCU Network Australia welcome applications for its 2016 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 2016: 31st January 2016 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)
- 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.
Applications should be sent to: The President, HCU Network Australia, PO Box 7484 BAULKHAM HILLS NSW 2153 or emailed to: firstname.lastname@example.org
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 www.debra.org.au