The Neurodegenerative Diseases Research Laboratory (NDRL) is dedicated to discovering the causes of and developing treatments for diseases that involve degenerative changes of the nervous system, including the retina, brain, spinal cord, and peripheral nerves. The laboratory is directed by Martin L. Katz, Ph.D. and Rebecca E.H. Whiting, Ph.D. and includes colleagues from the University of Missouri School of Medicine and College of Veterinary Medicine. The NDRL also works closely with other academic institutions, foundations, government agencies, and corporations to move therapies for neurodegenerative diseases from the laboratory to human applications.
A major focus of our research is on a group of rare inherited disorders known as lysosomal storage diseases. We study a specific group of lysosomal storage diseases called the neuronal ceroid lipofuscinoses (NCLs) or Batten disease. The NCLs result from mutations that cause impairments in the ability of cells to degrade specific molecules that are normally broken down in specialized intracellular organelles called lysosomes. In children with NCL, the inability of cells in the nervous system to degrade molecules that would normally be turned over results in eventual death of the cells. This is accompanied by neurological signs that can include blindness, seizures, and loss of cognitive abilities and control of movements. Over time, the debilitating effects of the NCLs become progressively worse and affected individuals invariably die young. To learn more about how the tragedy of Batten disease affects children and their families, visit the website of the Batten Disease Support and Research Association. We are working on enzyme replacement therapy, gene therapy, and cell implantation therapies to cure the NCLs.
In the course of our research we discovered Dachshunds that develop a type of NCL that is analogous to the human form called late-infantile NCL or CLN2 disease. CLN2 disease results from the lack of the ability of the body to make a protein called TPP1. Working with BioMarin Pharmaceutical Inc. we found that periodically infusing purified TPP1 protein into the cerebrospinal fluid of affected dogs significantly delays progression of the disease. The effects were so pronounced that based on these studies a test of this approach to therapy in affected children has been successfully completed, making this the first effective therapy available to children with this disease. We are also making significant progress in developing gene therapy approaches for treating this disease.
We also conduct mutation discovery research to identify the mutations that underlie any inherited neurodegenerative disease for which we can get the appropriate DNA samples. We are particularly interested in neurological diseases in dogs and cats. Our goals in identifying disease-causing mutations in these animals are both to provide breeders with DNA tests that they can use to avoid producing affected puppies or kittens, and to develop animal models that can be used to test therapies for the corresponding human disorders. Some of the diseases for which we have identified the underlying mutations are described in the Research section of this website. If you have a dog or cat that is exhibiting progressively worsening signs such as loss of coordination, mental decline, visual impairment, changes in personality, and/or seizures please contact Professor Katz.
If you have any questions about our research or would like to learn how you can assist with the research by providing us with samples or information, please contact us.