Gene Therapy for Late Infantile Neuronal Ceroid Lipofuscinoses (LINCL)
- 詳細技術說明
- Invention SummaryThis invention allows for the treatment of LINCL by intracranial administration of an adeno-associated virus (AAV) carrying the cDNA for the CLN2 gene.
- *Abstract
-
TechnologyOverview
LINCL is a type of Batten disease that is characterized by anautosomal recessive lysosomal storage disorder. Patients are first diagnosedaround the age of 2, presenting neurological symptoms such as seizures, ataxia,impaired vision, and speech and developmental problems. Afflicted children donot survive beyond 8-12 years of age. There is no known cure for this disease.
LINCL is caused primarily due to amutation in the CLN2 gene, which results in a deficiency in thetripeptidyl-peptidase I (TPP-I) enzyme product. Consequently, membrane proteinsaccumulate in lysosomes, appearing as autofluorescent, curvilinear lysosomalstorage bodies, leading to a loss of neurons, progressive neurological andretinal decline and blindness.
Previous studies have shown that invitro, addition of the pro form of TPP-I to cells obtained from LINCL patientsresults in transport of the protein to lysosomes, with a major decrease in theaccumulation of abnormal storage proteins. However, several challenges must beovercome in vivo, such as the inability of the protein to cross the blood-brainbarrier and potential toxicity issues associated with overexpression of TPP-I. The inventor, Dr. Ronald Crystal, a pioneer inthe field of gene therapy, has developed a treatment for the safe and sustaineddelivery of the pro form of TPP-I to LINCL patients via intracranialadministration, so as to decrease the severity of the disease, as well as todelay its onset and mortality rates.
Potential Applications
This gene therapy technique will provide much-needed treatment optionsfor patients with LINCL.
Advantages
· Once delivered to the CNS, this therapeutic approach willserve as a constant source of the pro form of TPP-I within the brain, thuseliminating the need for cumbersome, repetitive, invasive procedures.
· As low as 5-10% of endogenous TPP-I level restoration wouldbe sufficient to ameliorate severe phenotypes of the disease.
· When TPP-I is secreted into the CNS, it is capable ofcross-correcting neighboring cells, thus automatically increasing thedistribution of the protein, and raising the potential for success of thetherapy.
- *Licensing
- Brian J. Kelly, Directorbjk44@cornell.edu646-962-7045
- 其他
-
Publications
· Hackett N.R., et. al., Human Gene Therapy16:1484-1503 (2005)
· Clinical Protocol: Human Gene Therapy15:1131-1154 (2004)
- 國家/地區
- 美國
