Spotlight on Research - Dr. Gama Sosa

Read Dr. Gama Sosa's recently published article by the Nature Publishers in Gene Therapy

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Dr. Gama Sosa Miquel Gama-Sosa is the Associate Professor of Psychiatry Mt. Sinai School of Medicine Bronx V.A. Medical Center

Hunter’s Hope is excited to share with you the good news of Dr. Miquel Gama-Sosa’s recently completed successful research project, “Transgenic Rescue of Twitcher Mice.” The results of this work were presented at the 2003 Hunter’s Hope Scientific and Medical Symposium and soon will be published in Gene Therapy, a prestigious nature journal. Dr. Gama-Sosa is a two-time recipient of a Hunter’s Hope research grant.

First, a little background about Dr. Gama-Sosa: Born in Mexico City, he completed a major in Biology at the National School of Biological Sciences, and a research internship with Dr. Andrew Victor Schally, a Nobel laureate 1977 at Tulane University in New Orleans. After completing this short internship, he joined the graduate program in Biochemistry at and obtained his Ph.D. degree in 1985. Moving on to Harvard University, he furthered his research in the areas of retroviral promoter/enhancer regulation, HIV pathogenesis, the use of N-carboxymethylchitosan-O-sulfate as an anti-HIV agent and most important the development of murine recombinant retroviral systems for gene therapy. During his graduate years, he had the privileged of working with Dr. Emmanuel Shapira, a biochemical geneticist and a superb mentor, who introduced him to the field of inherited metabolic diseases.

Dr. Gama Sosa shares his professional career with his wife Dr. Rita De Gasperi, who has a life long record in glycolipid biochemistry, lysosomal enzymology and molecular genetics. In collaboration with many leading scientists they have identified and characterized several genetic dysfunctions responsible for several lysosomal diseases including the galactocerebrosidase deficiency of Krabbe disease. Results from this research are routinely being used in molecular diagnostic tests, carrier identification, prenatal diagnosis and population genetics. In addition, they were the first group to successfully revert the galactocerebrosidase deficiency of cells from a Krabbe patient using the recombinant retroviral vectors, which they had previously developed with Ruth Ruprecht at Harvard. These exciting experiments consisted in preparing infectious artificial retroviruses containing the human galactocerebrosidase cDNA to infect human fibroblasts from a Krabbe patient. The infected cells resulted in the stable de novo expression of galactocerebrosidase. Similarly, these recombinant viruses were also able to stably revert the galactocerebrosidase-deficient phenotype of cultured cells derived from the twitcher mouse (an authentic model of Krabbe disease). These results showed for the first time the possibility of reversing the galactocerebrosidase deficiency of Krabbe disease by gene therapy.

More recently, they have explored the possibility of reversing Krabbe disease in vivo in the twitcher mouse. As mentioned above, the twitcher mouse has long been known as an authentic model for human Krabbe disease. It has been and still is a very useful tool not only to better understand the biochemical and pathological basis of the disorder, but also to develop therapeutic strategies to correct in vivo the enzyme deficiency. Previous attempts at rescuing Krabbe disease in the twitcher mouse by bone marrow transplantation, viral transduction or transgenesis had been only partially successful. In collaboration with Dr. Gregory A. Elder, they have identified a bacterial artificial chromosome (BAC) containing the entire human galactocerebrosidase gene (>80 kB). Using this BAC, they have prepared transgenic twitcher animals harboring the entire human galactocerebrosidase gene via pronuclear injection into fertilized oocytes and selective mating. The resulting twitcher mice harboring the entire human galactocerebrosidase gene (twitcher hGALC tg mice) exhibited growth, motor function, and fertility similar to those of normal animals. The twitcher hGALC tg animals also had normal levels of galactocerebrosidase in the brain and were free of the typical twitcher demyelinating pathology. These mice have been maintained for over 1 year without any sign of disease, while the affected non-transgenic twitcher animals did not survive past 42 days. This work represents the first successful in vivo genetic treatment of Krabbe disease and opens the possibility of developing novel therapeutic approaches for the treatment of the disease in humans.

When asked, what the overall goal of his Krabbe disease research is, Dr. Gama-Sosa said That in addition to their genetic therapeutic approaches aimed at the treatment of Krabbe disease, they are exploring the use of biological factors to modify the inflammatory component of the disease in the twitcher mouse. It is the overall goal of his research to develop therapies in this animal model that may be extrapolated in the near future for the treatment of children affected with this devastating disease.

We are so grateful to Dr. Gama-Sosa for his work “Transgenic Rescue of Twitcher Mice.” At the 2003 Hunter’s Hope Scientific and Medical Symposium, Dr. Gama-Sosa presented his latest research findings, which provided him and other researchers additional time for collaboration. We are also grateful to all of our supporters that have made it possible for Hunter’s Hope to provide funding for this valuable research. Opportunities like these continue to help save the lives of future generations.

Working to raise money to fund research efforts to identify new treatments, therapies and a cure for Krabbe disease is the ultimate goal of our Foundation. With research, therapies and treatment continuing to progress for children born with Krabbe and the related leukodystrophies, sharing the news of our funded research projects helps us progress towards our ultimate goal. Thanks to our generous supporters, Hunter’s Hope has awarded approximately $3.7 million dollars towards valuable research projects in seven years. But while much work has been done on the leukodystrophy fronts, there is still much more to do.

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