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The development of therapy for Batten disease is at an early stage but is progressing.
The ultimate aim is a complete cure for all types of Batten disease. Along the way to achieving this might be the development of treatment that halts or delays the progression of some types of the disease. Successful therapy needs to reach the cells in the brain that die during the disease process, a difficult feat since the brain is specially protected from external influences. The eyes will also need to be treated. Effective treatments for systemic disease occurrign elsewhere in the body may also have to be developed.
Cell, mouse and larger animal models exist to test out new therapies as they are developed. A number of different approaches are being considered. The first successful therapies are likely to apply to those affected by mutations in CLN1, CLN2 or CTSD as these encode soluble enzymes.
Some clinical trials have begun. An up to date summary of all approed trials can be found at https://clinicaltrials.gov/
A clinic should provide published scientific literature on any procedure suggested. An experimental technique that is part of a scientific study/clinical trial should not result in a charge to families for taking part since expenses will be paid by those conducting the trial procedure.
Gene therapy
This is a way to deliver a corrected copy of the faulty gene into the cells that need it to function efficiently and correctly. Usually a modified viral vector is used to infect cells. Routes for delivery for this type of treatment might be via injection into the brain, requiring brain surgery; via a shunt into the CSF, the fluid which bathes brain cells; and via the blood supply using vectors that infect cells lining blood vessels. This approach is most likely to be effective for NCLs caused by mutation in genes encoding enzymes, as cells containing the corrected copy of the gene may be able to make enzyme that can be released and taken up by other cells not able to make the enzyme. The first tests used mouse models for CLN1 and CLN2. An important finding is that very early therapy (ie presymptomatic) provides best results. Further safety trials used improved vectors.
Stem cell therapy
This approach delivers cells that can make the correct version of the faulty protein. These cells could either deliver the correct enzyme to other cells or might even replace cells that die during the disease process.
Much work is needed before this approach can be considered a safe and effective treatment for NCL. For those considering this possibility, this site A closer look at stem cell treatments may provide some guidance on what to consider and what questions to ask any clinic suggesting this as a treatment for NCL. Certainly a clinic should provide published scientific literature on any procedure suggested. An experimental technique that is part of a scientific study/clinical trial should not result in a charge to families for taking part since expenses will be paid by those conducting the trial procedure.
Enzyme therapy
This approach delivers enzyme directly to the brain. Routes for delivery for this type of treatment might be via injection into the brain, requiring brain surgery; via a shunt into the CSF, the fluid which bathes brain cells; and via the blood supply, providing there is a way to transfer the enzyme across the blood-brain barrier.
A clinical trial showed that delivery of TPP1 enzyme into the brain is safe for children and a treatment for CLN2 disease, Brineura (Biomarin BMN-190 Cerliponase Alfa), is now approved by the EMA and FDA, and authorised in some countries.
Drug therapy
As more is discovered about changes that occur in the brain in NCL patients there may be drugs that will ameliorate these effects.
Drugs that allow read-through of mutations that introduce premature stops in NCL proteins (especially PPT1 and TPPI) have been considered. Drugs that help a mutated protein to fold correctly and regain activity, perhaps by increasing the amount of a key chaperone, are also under investigation. This approach is likely to be most suitable for proteins containing a missense mutation.
Immune therapy
The immune system seems to be affected, especially in juvenile NCL. So far no advantage is seen in treating patients with immunosuppressants.
Storage material degradation
It has been suggested that assisting cells to break down the accumulating storage material more efficiently would be beneficial. No benefit has yet been seen in patients.
Inhibition of cell death
Work to identify the different mechanisms that may cause cell death in brain cells of patients is underway. One drug reported to inhibit cell death is flupirtine, also used as an analgesic. Some patients now take this drug but no clinical trial has taken place, so it is not yet possible to be sure that it works.
Assessment of therapy
In order to assess the success of any therapy the expected progression of all types of the disease needs to be fully known (the natural history). Disease rating scales are used by several centres, and an International NCL patient Registry (DEM-CHILD) exists.
Genotype - phenotype correlations of LINCL
Clinical and neuropsychological investigations in Batten disease
Useful sites