Children born with genetic disorders can be a traumatic and heart breaking experience for parents. Due to lack of awareness and myths surrounding such disorders, many parents are often sent from pillar to post hoping to find an accurate diagnosis and possible cure for their afflicted child. Due to their failure to find alternative options and inability to afford whatever options are available, these unfortunate parents themselves end up as victims of psychosocial and poverty related issues.
Today, there’s a ray of hope for this much neglected inherited community, with the first free of charge Neurogenetic testing facility in the state sector being set up at the University of Sri Jayewardenepura (USJ).
Founder of the Interdisciplinary Center for Innovation in Biotechnology and Neuroscience, USJ and Research Prof, KDU-CARE, General Sir John Kotelawala Defence University Ranil de Silva tells the Sunday Observer how the ICIBN and KDU can provide much needed genetic diagnosis referred by the panel of neurologist to help parents seeking Genetic testing.
Excerpts:
Q. With the sharp rise in Non Communicable Diseases (NCDs) new diagnostic methods are now being developed to nip early development of diseases like Diabetes type 2, cancer, cardiac problems, hypertension, stroke. With the present government’s commitment to drastically reduce the incidence of NCDs which have now overtaken the number of communicable diseases in Sri Lanka within the next few years, tell us how Genetic testing can contribute to this goal. Since many still don’t know or have even heard of it, tell us what is Gene testing? Why is it important?
A. NCDs are considered the most feared killer, responsible for 70 precent of all deaths, and the main threat to the sustainability of health systems. Increasing evidence indicates a genetic role in major NCDs, including cancer, diabetes, cardiovascular diseases, mental health and asthma. In cancer and cardiovascular disease research, new loci mutations are being discovered in connection with disease development, especially, pertinent in breast, colon, and prostate cancers as well as atherosclerosis and hypercholestrolemia where a significant percentage of these mutations are familial or inherited.
The expanding knowledge of the genetic basis, pathogenesis, and therapeutic possibilities of NCDs has provided new targets for early diagnosis of human diseases, drug discovery, and drug development and suggested strategies to translate this knowledge into clinical practice as (initial) clinical trials. Biomarkers represent a measurable biological indicator able to provide information on risk assessment, diagnosis, and therapy for NCDs. Omic sciences (genomic, transcriptomics, proteomics, metabolomics) offer opportunities to identify novel biomarkers for defining and understanding the molecular basis of NCDs, which I have already started with the University of Houston .
Q. As a specialist in the field, tell us what is genetic disorder?
A. A Genetic disorder is a health problem caused by one or more abnormalities in the genome. The mutation responsible can occur spontaneously (without a family history) before embryonic development, or it can be inherited from two parents who are carriers of a faulty gene (autosomal recessive inheritance) or from a parent with the disorder (autosomal dominant inheritance).
Q. Are genetic disorders a common health issue in Sri Lanka? What is the percentage islandwide?
A: More than 7·5 million children are born annually with either a severe genetic disorder or a birth defect, and nearly 95 percent of them live in low-income or middle-income countries. Thalassemia is by far the most common single-gene disorder in Sri Lanka. The inherited disease community remains as a highly neglected cluster within Sri Lanka.
Q. What will happen if they remain undiagnosed ? Where can they be tested if they show symptoms?
A. In many cases patients with a neurogenetic disease die without proper genetic diagnosis partly due to limited facilities. Inaccessibility, unaffordability and lack of awareness has been reported.
Q. When children are diagnosed with a genetic disorder care givers and parents are often those who bear the brunt of adverse reactions to the news. Is this correct?
A. Parents suffer when a child is diagnosed with a genetic disease. Mothers experience self-blame and pressure from their in-laws because they are branded as the root cause of their child’s disorder. Parents also express a fear of having more children. Due to lack of communication with medical practitioners, they fail to find out about alternative methods, such as adoption. However, the lack of availability and affordability limits the exploration of these options even when known. The pathetic plight of psychosocial and poverty issues faced by these patients have been accepted to be published in the Annals of Neurosciences by us.
Q. What are the options open to them? Where can they get them?
A. At present, molecular analysis, and genetic testing for neurogenetic diseases are primarily being conducted as a costly service, by the private sector of Sri Lanka.
Q. Explain the process involved in Gene therapy and how it benefits the recipients.
A. Gene therapy is an experimental technique that uses genes to treat or prevent, where a healthy gene is introduced to a patient. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein.
Though most genetic neurological disorders are currently minimally responsive to existing pharmacological treatments, they are potential candidates for Gene therapy. Gene therapy may revolutionise the treatment of neurological disorders in the coming decades but there are still great challenges ahead. The treatment of genetic disorders - Gene-Based Therapy is an ongoing battle, with clinical trials having been completed, others are ongoing, or have been approved worldwide.
Q. Molecular genetic testing has been described as the ‘gold standard’ in the diagnosis of genetic diseases. Your comments?
A. Since disease diagnosis based on clinical symptoms and nongenetic laboratory findings, has limited sensitivity and specificity, the focus is now placed on early diagnosis and anticipatory treatment strategies addressing expected and potentially modifiable disease complications through early Genetic diagnosis.
Q. What is your success rate? Any feedback?
A. To date ICIBN has been successful in providing free Genetic Diagnostic Reports to over 500 patients nationwide, worth over rupees four million to the patients, to facilitate accurate diagnosis and timely patient management of diseases such as Duchenne Muscular Dystrophy (DMD), Spinocerebellar Ataxias (SCA), Huntington’s Disease (HD), Spinal Muscular Atrophy (SMA), Limb Girdle Muscular Dystrophy (LGMD) and Myotonic Dystrophy.
This was only possible due to the untiring and dedicated efforts of PhD candidates Nalaka Wijekoon and Lakmal Gonawala, and a team of clinical doctors including Dr. Pulasthi Dissanayake.
The success story and the road map of establishing cost effective molecular diagnostic facility in a developing country has been accepted for publication as a benchmark article in the reputed journal “Lancet Neurology”; ranking first among clinical neurology journals. . Genetic diagnostics was established with the support of the then Minister of Science and Technology Keheliya Rambukwella and the National Institute of Health, USA.
Q. How do you follow up on your patients?
A. The ICIBN team has been visiting hospitals almost in all parts of the country to examine the patients by a standard method and perform genetic testing for better availability and convenience of patients, bestowing a unique barefoot service to the nation in collaboration with the consultant neurologists/ paediatric neurologists from hospitals across the island.
Q. What are ICIBN’s plans for the future?
A. With disease-modifying treatments, Gene-Based therapies approved by the US Food and Drug Administration (FDA), a significant investment will be necessary for the development of clinical expertise and infrastructure for the long-term administration of a treatment like Antisense Oligo Nucleotides (ASOs).
Therefore, we have established a rapport with personalised drug development companies where Sri Lanka has been successfully identified as a potential study site for Phase 3 clinical trials, resulting in the aforementioned exorbitant personalised medicine being available free for eligible patients in the upcoming years. This initiative will be a “Ray of Hope in the Darkness” for the inherited rare disease community in Sri Lanka.
Q. Briefly spell out its goals.
A. The ICIBN goal is dedicated to the Genetic Disease Diagnostics, research and training personnel to make genetic testing readily available. This provides the much needed genetic information for gene therapy, with the following objectives:
• Providing molecular diagnostic and treatment options (gene therapy) for patients with selected genetic disorders of neurological and neuromuscular disorders, through public-private partnerships
• Advocating for:
• Newborn screening,
• Prenatal testing - Testing at pregnancy to determine whether an unborn child is affected, is possible with genetic testing in an affected family
• Carrier testing
• Training personnel for genetic testing leading to obtain double doctorates, which I initiated at USJ with prestigious foreign universities. This is a new chapter in the field of double Doctoral studies in Sri Lanka where Ms. Printha Wijesinghe has been awarded the first Double Doctorate from Maastricht University, Netherlands.
Two PhD students are now fully trained to take over genetic diagnosis.
Public Policy development/implementation to cover patients with rare, undiagnosed and genetic diseases has been initiated, such as Rare Disease Policy and Orphan Drug Policy with the Ministry of Health.
We also plan to connect over 70 million patients globally with international collaboration to facilitate and encourage research, orphan drug development activities and finding new genes.
Q. Any other new avenues you are exploring for the not too distant future?
A. PhD students at ICIBN, in addition to genetic testing are looking into the effect of our own natural products e.g. Ceylon cinnamon and Ceylon tea, in collaboration with the Ministry of Agriculture on disease-modifying treatments on neurogenetic disease. Prompt and rapid diagnosis is essential, as early initiation of treatment leads to improved outcomes.
Hence, carrier screening and newborn screening is recommended so that proactive treatment with gene therapy could be implemented as soon as it reached the genetic diagnosis in pre symptomatic infants and strengthened the rationale for newborn screening.
In addition, Yoonus Imran, Ph.D. scholar is working on genetic characterisation (DNA barcoding) of herbs and natural products (i.e Ceylon cinnamon) for the development of scientifically validated and value added Neuro-Nutraceuticals.
Q. How are you funded?
A. Genetic testing and research has been funded solely by foreign and local donations and research grants that I have received. State support if provided to the established biobank could lead to a biotechnology hub in South Asia, providing genetic testing service to SAARC countries.
Q. Summarise how genomic medicine in routine clinical practice can improve care of Lankan patients?
A. It would facilitate improved care for patients, enabling Sri Lankan doctors to diagnose and successfully manage patients with a spectrum of rare disorders with coexisting phenotypes.
The approach will build a catalogue of genetic variants in the Sri Lankan population. Integrating medical genetics into the primary health care services and improving accessibility to genetic diagnostics and counselling services outside of Colombo also need to be addressed.
Q. Your message to parents of children with genetic disorders
A. There is a ray of hope for gene therapies. However, achieving such goal is not an easy task, where medicine and science should amalgamate for a better solution. Together we can make a difference.