All the genetic information contained in a person’s DNA is known as their genome, which is made up of about 19,000 genes. While genes are mostly the same in all people, every person has small variations in their genes. Genetic differences make each of us unique. They can also be the cause of inherited genetic diseases. Genetic mutations acquired over time can cause cancer. Genetic differences also account for individuals reacting differently to various drug therapies.
Today, genome sequencing is faster and more affordable than ever. This creates opportunities for researchers to develop tools that will help clinicians predict which therapies and drugs will be safest and most effective for each patient, based on information contained in their genome. This is the promise of Genomics-guided Precision Medicine.
This work requires a range of expertise and infrastructure that spans research bench to patient bedside, including:
- Clinicians who can identify patients who have suffered ADRs
- Researchers who collect in-depth clinical information on each patient
- Geneticists who use leading-edge genomics technologies to examine the DNA of patients
- A range of professionals from many disciplines including pharmacologists, statisticians, nurses, regulators and policy makers
Example: Dr. Ross developed a gene therapy treatment for lipoprotein lipase (LPL) deficiency, a genetic disease that causes extremely elevated triglycerides in blood and life-threatening pancreatitis. This new therapeutic strategy delivers the LPL gene into patient cells using engineered adeno-associated virus (AAV) particles. Dr. Ross developed and then optimized this treatment in animal models (Ross et al., 2004, 2005, 2006a, 2006b). Clinical trials in LPL-deficient patients demonstrated the long-term safety and effectiveness of the treatment (Stroes et al., 2008; Gaudet et al., 2012, 2016).
This new treatment (Glybera®, alipogene tiparvovec) received regulatory approval in late 2012 (“First gene therapy approved”, Nat Biotech, 2012) and this has helped revitalize the gene therapy field (“End of the Beginning of Gene Therapy” Flotte, Hum Gene Ther, 2015). The commercialization of this research (uniQure Inc.) was recognized in MIT Tech Review’s list of 50 most innovative companies.
- Kastelein, J, Ross, C.J.D., & Hayden, MR. From mutation identification to therapy: discovery and origins of the first approved gene therapy in the Western world. Hum Gene Ther. 2013 May;24(5):472-8. PMID: 23578007.
- Stroes ES, Nierman MC, Meulenberg JJ, Franssen R, Twisk J, Henny CP, Maas MM, Zwinderman AH, Ross C.J.D., Aronica E, High KA, Levi MM, Hayden MR, Kastelein JJ, Kuivenhoven JA. Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients. Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2303-4. PMID: 18802015.
- Ross, C.J.D., Twisk, J. Meulenberg, J.J.M., Kuivenhoven, J.A., Miao, F., Scheenhart-van der Meer, J.W.C, Moraal, E., Oranje, P.P.A., Hermens, W.T..J.M.C., Kastelein, J.J.P., Hayden, M.R. Correction of Feline Lipoprotein Lipase Deficiency with AAV1-mediated gene transfer of the naturally-occurring LPLS447X beneficial mutation. Gen. Ther. 2006. 17(5):487-99. PMID: 16716106.
- Ross, C.J.D., Twisk, J., Kuivenhoven, J.A., Rip, J., Kastelein, J.J., and Hayden, M.R. Gene Therapy with Lipoprotein Lipase Variant S447X. Arterioscler. Thromb. Vasc. Biol. 26: 25-28. 2006. PMID: 16484602. (FA)
- Ross C.J.D., Liu, G., Kuivenhoven, J.A., Twisk, J., Rip, J., van Dop, W., Ashbourne Excoffon, K.J., Lewis, S.M., Kastelein, J.J., Hayden, M.R. Complete Rescue of Lipoprotein Lipase-Deficient Mice by Somatic Gene Transfer of the Naturally Occurring LPLS447X Beneficial Mutation. Thromb. Vasc. Biol. 25(10):2143-50. October 2005. PMID: 16002740.
- Ross, C.J.D., Twist, J., Meulenberg, J.J.M., Liu, G., Van Den Oever, K. Moraal, E., Hermens, W.T., Rip, J., Kastelein, J.J.P., Kuivenhoven, J.A., Hayden, M.R. (2004) Long-term correction of murine Lipoprotein Lipase Deficiency with AAV1-mediated gene transfer of the naturally-occurring LPLS447X beneficial mutation. Human Gene Therapy, 15 (9) 906-919, September, 2004. PMID: 15353045.
- Kay et al., The Targetable A1 Huntington Disease Haplotype has Distinct Amerindian and European Origins in Latin America. European Journal of Human Genetics. 2017 Feb;25(3):332-340.
- Kay et al., Huntingtin Haplotypes Provide Prioritized Target Panels for Allele Specific Silencing in Huntington Disease Patients of European Ancestry. Molecular Therapy. 2015 Nov;23(11):1759-71