The use of 3-methoxy-pregnenolone for the preparation of a drug for treating a traumatic brain injury

Abstract

A method for the treatment of a traumatic brain lesion comprises administering to the patient an effective quantity of 3β-methoxy-pregna-5-ene-20-one (3β-methoxy-PREG).

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of, and claims priority from, U.S. Ser. No. 12 / 232,993 filed Sep. 26, 2008, which is a continuation-in-part of, and claims priority from, U.S. Ser. No. 10 / 542,495 filed Jul. 15, 2005, which claims priority under 35 U.S.C. 371 from PCT / FR04 / 00086 filed on Jan. 16, 2004, which claims priority from French application No. 0300507 filed on Jan. 17, 2003. The content of each of the prior applications are incorporated herein by reference.TECHNICAL FIELD[0002]The invention involves an innovative use of neurosteroid derivatives, notably pregnenolone and pregnenolone derivatives, to treat nervous system lesions, in particular a traumatic spinal cord or brain lesion, and certain neurodegenerative diseases, notably linked to the ability of the aforementioned neurosteroid derivatives to stabilize and / or increase the polymerization of neuronal microtubules. The invention further relates to the therapeutic use...

AI Technical Summary

Benefits of technology

[0056]In a preferred embodiment, and notably to treat diseases related to a central nervous system disturbance, the aforementioned drug also comprises an excipient or a compound that makes it possible to formulate the aforementioned 3-methoxy-PREG such that it crosses the blood-brain barrier better. Such an excipient or compound can also make possible a faster or more long-lasting crossing of the aforesaid blood-brain barrier.

Problems solved by technology

Neurodegenerative diseases and CNS lesions such as spinal cord and brain injuries are widespread conditions with devastating effects on the life of the patients and their close relatives.

Almost more dramatically, about 2,000,000 US people undergo each year a traumatic brain injury (TBI), whose immediate as well as long term consequences are largely underestimated and deprived of medical solution.

Long term consequences of TBI include mood disorders, sleep disorders, cognitive defects, memory loss, locomotor disabilities and occur very frequently unrespectively of the initial severity of the trauma.

At the biological level, TBI provokes widespread shearing and stretching of nerve fibers (diffuse axonal injury) and leads to destabilization of neuronal microtubules, disruption of the cytoskeleton, dendrite atrophy and loss of MAPs.

The functional consequences of dendritic damage are reflected in reports of compromised efficacy of synaptic transmission following TBI.

After TBI, a spontaneous and partial recovery of lost function can occur over time although axonal regeneration is extremely limited in the mammalian adult central nervous system.

Despite many research efforts in the field, effective molecules for the treatment of neurodegenerative diseases and CNS lesions are still not available.

This deterioration can be the consequence but also the cause of damage to the affected cells.

However, the synthesis of MAP2 proteins is not in and of itself sufficient to induce this dendritic growth process.

Importantly, the MAP2 / TAU loss and microtubule depolymerization observed in spinal cord and brain injury can be directly responsible for the dysfunction of certain neurons and can result in their death.

Moreover, such cytoskeletal deterioration can affect the number and the length of the neuritic extensions of the remaining neuronal cells and, as a consequence, decreases their effectiveness.

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