Gene Therapy

There is currently no specific treatment for BCM, but recent progress made by gene therapy on a number of diseases of the retina (Leber’s congenital amaurosis and choroideremia) makes this disease a potential candidate. The BCM Families Foundation and Applied Genetic Technologies Corporation (Nasdaq:AGTC), a biotechnology company conducting human clinical trials of adeno-associated virus (AAV)-based gene therapies for the treatment of rare eye diseases, started in 2016 a collaboration to develop an AAV-based gene therapy for BCM.

Gene therapy consists of an injection into the retina, using as a vector a virus unable to replicate (and therefore unable to cause damage) to introduce a specific gene into the cells of the patient.
The name of the virus is adeno-associate virus, AAV. AAV is a small virus which infects humans and some other primate species. AAV is not currently known to cause disease and consequently the virus causes a very mild immune response. Gene therapy vectors using AAV can infect both dividing and quiescent cells.

The virus injected into the retina infects the cones, into which it introduces the correct gene sequence, the same sequence contained in healthy individuals. This sequence does not replace the mutated copy of the gene into the nucleus of the cones of the patient, but introduce the missed protein inside the out segment of the cones.

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Step 1: Scientists modify an adeno-associated virus (AAV), a common virus that is not known to cause any disease in humans, by stripping out what’s on the inside of the virus and replacing that with a functioning copy of a L-opsin or M-opsin gene.

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Step 2: When doctors inject intravitreally the modified (AAV) vector in a patient’s eye, it travels into the patient’s retinal cones cells. Once inside cones, the vector passes on the functioning copy of the L-opsin or M-opsin gene the BCM patient needs, which was harbored in the AAV vector.

This correction carried out using gene therapy is not “passed on” to children and grandchildren, so affected individuals in the following generations must repeat the treatment.

In the case of Leber’s congenital amaurosis and choroideremia, following laboratory studies and tests on animal models, clinic trials were started, during which numerous patients from different countries were successfully treated.

For BCM, scientists have created an animal model, on which they are starting to test the gene therapy.

To learn more about AAV and gene therapy of the human please click here.

BCM Animal Model

Here you find research papers about animal model with disease similar to BCM:

Xie B, Nakanishi S, Guo Q, Xia F, Yan G, An J, Li L, Serikawa T, Kuramoto T, Zhang Z. A novel middle-wavelength opsin (M-opsin) null-mutation in the retinal cone dysfunction rat. Exp Eye Res. 91(1):26-33, 2010.

Zhang, Z., Pang, J., Xia, F., Guo, Q., Li, L., An. J., Zhang, L., Hauswirth, W.W., Yang, S., Li, Z.
‘AAV-mediated Gene Therapy Restores Cone Function In A Rat With An M-cone Opsin Deficiency. A Model For Blue Cone Monochromacy’

Here you find a gene therapy result about color blindness in adult primates:

Mancuso K, Hauswirth WW, Li Q, Connor TB, Kuchenbecker JA, Mauck MC, Neitz J, Neitz M, ‘Gene therapy for red-green colour blindness in adult primates’. Nature 2009;461:784-787.

Katherine Mancuso, Matthew C. Mauck, James A. Kuchenbecker, Maureen Neitz, and Jay Neitz ‘A Multi-Stage Color Model Revisited: Implications for a Gene Therapy Cure for Red-Green Colorblindness’. 2010 R.E. Anderson et al. (eds.), Retinal Degenerative Diseases, Advances in Experimental Medicine and Biology 664.