Other Therapeutic Approaches

A newer therapeutic approach is the administration of betaine (6-12 g daily), which lowers homocysteine levels by favoring remethylation [33], A theoretical hazard of betaine treatment is increasing the blood methionine, sometimes to an extravagant degree ( 1 mmol/1). Experience to date indicates that betaine administration is safe, with no major side effects except for a fishy odor to the urine. Other therapeutic approaches have included the administration of salicylate to ameliorate the thromboembolic diathesis. Patients also have been treated with dietary supplements of L-cystine, since the block of the transsulfura-tion pathway in theory could diminish the synthesis of this amino acid. 

Eor many years, lithium salts have been used for maintenance treatment. However, naturalistic studies have reported a relatively high failure rate in patients on lithium and therefore other therapeutic approaches have been considered. 

Randomization and blinding important where effects cannot be measured objectively. Safety assessment relative to the disease to be treated, in comparison with other therapeutic approaches, considering the characteristics of sub-groups of patients, and considering the animal toxicology and pharmacology data. 

Plasmapheresis is an intermediate form of therapy for myasthenia gravis, having effects that last longer than those of cholinesterase inhibitors but shorter than those of thymectomy. Improvement in myasthenic symptoms often occurs, but its duration is unpredictable. Plasmapheresis usually is reserved for patients who have severe symptoms resistant to other therapeutic approaches or for patients preparing for thymectomy. 

In man, transplantation carries a number of risks associated with an invasive technique but offers a longer-term solution to enzyme infusion. The relatively few clinical reports suggest that this may be an option when other therapeutic approaches are unavailable. 

Other therapeutic approaches that are used Include ileal bypass which was reviewed by Gomes et They suggest that this treatment should only be considered if conventional procedures described above are unsuccessful. Aortocoronary bypass as an emergency measure has also been suggested with reservations for acute cases of myocardial infarction. ... 

Chemotherapy with asparaginase has been limited by the small available supply of this enzyme and by hypersensitivity reactions reported with crude enzyme preparations. The qualitative biochemical difference in the asparagine metabolism of neoplastic and normal tissues suggests other therapeutic approaches. For example, drugs should be sought that selectively inhibit asparagine utilization and biosynthesis in tumors. ... 

The other therapeutic approach to treat cancers is to block the expression of certain oncogenes such as C-raf and C-ras and kinases. The antisense oligonucleotide strategy is focused on blocking the activity of these genes. However, oligonucleotides are unstable in the body and are not taken up very efficiently by the cells. Nanospheres could facilitate the uptake of... 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

In humans, poor sleep correlates with low plasma melatonin and can be improved by melatonin administration. This therapeutic approach has been tried especially in individuals whose sleep rhythms are disrupted by shift-work, blindness or jet-lag but its benefits are as yet unconfirmed and, in any case, the mechanisms by which it might reset sleep patterns are unclear. Of course, it must be remembered that other body... 

Examples abound regarding the role of serendipity in the discovery of new therapeutic approaches, which on closer examination usually turned out to be the result of clinicians paying attention to unexpected clinical effects rather than discounting them. For example, lithium was tried first for hypertension, chlorpro-mazine was initially developed as an anesthetic, and imipramine was originally regarded as an antihistamine and an antipsychotic agent. Without astute clinical observations, these drugs would not have found their niche, nor would clozapine have been revived for the benefit of millions of the most difficult to treat schizophrenic patients. Other examples include the expanded indications of newer... 

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