Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplantation of Schwann cells (SCs) has been extensively investigated as a therapeutic intervention in rodent models of spinal cord injury (SCI). Here we review both strengths and weaknesses of this approach and discuss additional strategies for maximizing the potential of SCs to repair the injured spinal cord. With no additional treatments, SCs were consistently shown to provide a bridge across the lesion site, supporting the ingrowth of sensory and propriospinal axons, to myelinate axons and to decrease the size of cavities formed after injury. Supraspinal axons did not, however, grow onto the bridge, axons failed to traverse the caudal SC-host cord interface and transplanted SC survival was poor. More recent studies have shown that the potential of SC transplantation as a therapeutic approach can be strongly enhanced by combining additional strategies . For example, combining SC transplantation with elevation of cAMP levels resulted in growth of brainstem axons into the SC graft and caudal to the lesion and in significant improvements in locomotion. Axon growth (and functional improvement) have been increased by strategies to raise neurotrophin levels, either by injection or by genetic modification of the SCs before transplantation. A major problem in maximizing SC potential in injured cord has been in achieving good integration of the transplanted cells with the adjacent cord parenchyma. Several previous studies suggested an ability of SCs to migrate extensively in CNS tissue when astroctyes were absent and to myelinate CNS axons. Furthermore, in some cases involving very limited injury, SCs migrated and integrated well even in the presence of host astrocytes. Consistent with these observations, treatments with an enzyme, chondroitinase, to modify the SC-astrocyte interface surrounding the graft, have shown much promise. Very new studies have shown that SCs derived from SC precursors show a higher ability to survive, integrate well with host tissue and support brainstem axon growth into and beyond the graft, confirming the innate promise of SCs in spinal cord repair. We review one clinical trial already underway in Iran testing SC transplantation in patients with SCI. Finally, we briefly describe a protocol, adaptable to the principles of good manufacturing practice, for generating large numbers of human SCs. Overall, the available evidence suggests that SCs, especially when used in combination with other treatments, offer one of the best hopes we have today of devising an effective treatment for spinal cord repair.
 ...
PMID:Realizing the maximum potential of Schwann cells to promote recovery from spinal cord injury. 2309 34

Schwann cells (SCs), when implanted in the injured spinal cord, support regeneration of axons, myelinate or ensheathe regenerated axons in a normal way, reduce cyst formation in the injured tissue, reduce secondary damage of tissue around the initial injury site, and modestly improve limb movements. If SC transplantation is combined with additional treatments such as methylprednisolone, neurotrophins, GDNF, olfactory ensheathing cells, chondroitinase, or elevation of cAMP levels, more axons (including those from neurons in the brainstem) regenerate into and out of the SC implant and further improve locomotion. Recent work to improve SC migration from the implant into the spinal cord by polysialylating NCAM on the SC surface has led to the novel finding that corticospinal axon growth is promoted by SCs. Recent studies are cited showing that when astrocytes extend slender processes into an implant instead of forming a sharp boundary they are permissive rather than inhibitory to axonal regrowth. The interfaces that comprise the "on-ramps" and the "off-ramps" are key to the success of a SC implant to span the injury site and to foster axon regeneration across the injury.
 ...
PMID:Schwann cell transplantation: a repair strategy for spinal cord injury? 2318 20

Peripheral nerve injury is common especially among young individuals. Although injured neurons have the ability to regenerate, the rate is slow and functional outcomes are often poor. Several potential therapeutic agents have shown considerable promise for improving the survival and regenerative capacity of injured neurons. These agents are reviewed within the context of their molecular mechanisms. The PI3K/Akt and Ras/ERK signaling cascades play a key role in neuronal survival. A number of agents that target these pathways, including erythropoietin, tacrolimus, acetyl-l-carnitine, n-acetylcysteine and geldanamycin have been shown to be effective. Trk receptor signaling events that up-regulate cAMP play an important role in enhancing the rate of axonal outgrowth. Agents that target this pathway including rolipram, testosterone, fasudil, ibuprofen and chondroitinase ABC hold considerable promise for human application. A tantalizing prospect is to combine different molecular targeting strategies in complementary pathways to optimize their therapeutic effects. Although further study is needed prior to human trials, these modalities could open a new horizon in the clinical arena that has so far been elusive.
...
PMID:Improving peripheral nerve regeneration: from molecular mechanisms to potential therapeutic targets. 2522 Jun 11

This study describes the use of poly(propylene carbonate) (PPC) electrospun microfibres impregnated with a combination of dibutyryl cyclic adenosine monophosphate (db-cAMP) and chondroitinase ABC (ChABC) in the treatment of right-side hemisected spinal cord injury (SCI). Release of db-cAMP and/or ChABC from the microfibres was assessed in vitro using high-performance liquid chromatography (HPLC). Drug-impregnated microfibres were implanted into the hemisected thoracic spinal cord of rats, and treatment was evaluated using functional recovery examinations and immunohistochemistry. Our results demonstrated that the microfibres containing db-cAMP and/or ChABC displayed a stable and prolonged release of each agent. Sustained delivery of db-cAMP and/or ChABC was found to promote axonal regenerative sprouting, functional recovery, and reduced glial scar formation when compared to untreated control animals. The combination of both db-cAMP and ChABC was determined to be more effective than using either drug alone in the treatment of SCI. These findings demonstrate the feasibility of using PPC electrospun microfibres for multi-drug combination therapy in SCI.
 ...
PMID:The combination of db-cAMP and ChABC with poly(propylene carbonate) microfibers promote axonal regenerative sprouting and functional recovery after spinal cord hemisection injury. 2801 83


<< Previous 1 2