Peripheral Neuropathies: Will Growth Factors Be Effective as Therapies?

Abstract

Neurotrophic factors are proteins that promote the survival and differentiation of specific neuronal popula tions. With the successful cloning and large-scale production of many different neurotrophic factors, it has become practical to consider their application in the treatment of neurological disease. Several categories of neurotrophic factors hold particular promise for the treatment of peripheral neuropathy in the near future. Preclinical studies have demonstrated the potential utility of factors like nerve growth factor for the treatment of small-fiber peripheral neuropathy and, possibly, compressive sensory neuropathies. Brain-derived neu rotrophic factor, ciliary neurotrophic factor, and insulin-like growth factor-I are likely to be applied in the treatment of motor neuropathy. Neurotrophin-3 has particular promise for the treatment of large-fiber sensory neuropathy. Although, for the most part, neurotrophic factors do not appear to have major toxicity, they represent a new class of drugs and clinical trials must proceed with caution. Clinical trials of several of these growth factors are currently underway, and others are being planned. The Neuroscientist 1:176-182, 1995

Keywords

KEY WORDS Neurotrophic Nerve growth factors Neuropathy Penpheral nerve

Get full access to this article

View all access options for this article.

References

Cohen S. , Levi-Montalcini R. , Hamburger V. A nerve growth stimulating factor isolated from sarcomas 37 and 180 . Proc Natl Acad Sci U S A 1954;40:1014-1018.

Levi-Montalcim R. The nerve growth factor 35 years later. Science 1987;237:1154-1162.

Leibrock J. , Lottspeich F. , Hohn A. , et al. Cloning and expression of brain derived neurotrophic factor . Nature 1989; 341:149-152.

Eide FF , Lowenstein DH , Reichardt LF Neurotrophins and their receptors —current concepts and implications for neurologic disease. Exp Neurol 1993;121:200-214.

Maisonpierre PC , Belluscio L. , Squinto S. , et al. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 1990;247:1446-1451.

Rosenthal A. , Goeddel DV , Nguyen T. , et al. Primary structure and biological activity of a novel neurotrophic factor. Neuron 1990 ;4:767-773.

Hallbook F. , Ibanez CF , Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 1991;6:845-858.

Berkemeier LR , Winslow JW , Kaplan D. , et al. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron 1991;7:857-866.

Gotz R. , Koster R. , Winkler C. , et al. Neurotrophin-6 is a new member of the nerve growth factor family . Nature 1994;372:266-269.

10.

Adler R. , Landa KB , Manthorpe M. , Varon S. Cholinergic neurotrophic factors: intraocular distribution of soluble trophic activity for ciliary neurons. Science 1979 ;204:1434-1436.

11.

Skapper SD , Varon S. Age dependent control of dorsal root ganglia neuron survival by macromolecular and low molecular weight trophic agents and substratum bound laminins. Brain Res 1986;389:39-46.

12.

Blottner D. , Bruggemann W. , Unsicker K. Ciliary neurotrophic factor supports target-derived preganglionic sympathetic spinal cord neurons . Neurosci Lett 1989;105:316-320.

13.

Kotzbauer PT , Lampe PA , Estus S. , Millbrandt J. , Johnson EM Jr. Postnatal development of survival responsiveness in rat sympathetic neurons to leukemia inhibitory factor and ciliary neurotrophic factor. Neuron 1994;12:763-773.

14.

Oppenheim RW , Prevette D. , Qin-Wei Y. , Collins F. Control of embryonic motoneuron survival in-vivo by ciliary neurotrophic factor. Science 1991 ;251:1616-1618.

15.

Bazan JF Neuropoietic cytokines in the hematopoietic fold. Neuron 1991;7:197-208.

16.

Ip NY , McClain J. , Barrezueta NX , et al. The α component of the CNTF receptor is required for signalling and defines potential CNTF targets in the adult and during development. Neuron 1993;10:89-102.

17.

Near SL , Whalen LR , Miller JA , Ishii DN Insulin like growth factor II stimulates motor nerve regeneration . Proc Natl Acad Sci U S A 1992;89:11716-11720.

18.

Kanje M. , Skottner A. , Sjoberg J. , Lundborg G. Insulin like growth factor I (IGF-I) stimulates regeneration of the rat sciatic nerve. Brain Res 1989;486:396-398.

19.

Glazner GW , Lupien S. , Miller JA , Ishii DN Insulin like growth factor-II increases the rate of sciatic nerve regeneration in rats. Neurosci 1993;54:791-797.

20.

Recio-Pinto E. , Rechler MM , Ishii DN Effects of insulin, insulin like growth factor—II, and nerve growth factor on neurite formation and survival in cultured sympathetic and sensory neurons. J Neurosci 1986;6:1211-1219.

21.

Ang LC , Bhaumick B. , Munoz DG , Sass J. , Juurlink Bhj. Effects of astrocytes, insulin and insulin like growth factor I on the survival of motoneurons in-vitro. J Neurol Sci 1992 ;109:168-172.

22.

Strand FL , Rose KJ , King JA , Segarra AC , Zuccarelli LA ACTH modification of nerve development and regeneration. Prog Neurobiol 1989;33:45-85.

23.

DeKoning P. , Gispen WH Org 2766 improves functional and electrophysiological aspects of regenerating sciatic nerve in the rat. Peptides 1987;8:415-422.

24.

Johnson EM Jr. Destruction of the sympathetic nervous system in neonatal rats and hamsters by vinblastine: prevention by concomitant administration of nerve growth factor. Brain Res 1978;141:105-118.

25.

Windebank AJ , Smith AG , Russell JW The effect of nerve growth factor, ciliary neurotrophic factor, and ACTH analogs on cisplatin neurotoxicity in-vitro . Neurology 1994;44:488-494.

26.

Konings Pnm , Makkink WK , van Delft Aml , Ruigt Gsf. Reversal by NGF of cytostatic drug reduction of neurite outgrowth in dorsal root ganglia in-vitro . Brain Res 1994;640: 195-204.

27.

Hayakawa K. , Sobue G. , Itoh T. , Mitsuma T. Nerve growth factor prevents neurotoxic effects of cisplatin, vincristine and taxol on adult rat sympathetic explants in-vitro . Life Sci 1994;55:519-525.

28.

Apfel SC , Lipton RB , Arezzo JC , Kessler JA Nerve growth factor prevents toxic neuropathy in mice. Ann Neurol 1991;29:87-89.

29.

Apfel SC , Arezzo JC , Lipson L. , Kessler JA Nerve growth factor prevents experimental cisplatin neuropathy. Ann Neurol 1992;31:76-80.

30.

Miyata Y. , Kashihara Y. , Homma S. , Kuno M. Effects of nerve growth factor on the survival and synaptic function of Ia sensory neurons axotomized in neonatal rats. J Neurosci 1986;6:2012-2018.

31.

Straznicky C. , Rush RA The effect of nerve growth factor on developing primary sensory neurons of the trigeminal nerve in chick embryos . Anat Embryol 1985;171:91-95.

32.

Apfel SC , Dormia C. , Newell ME , Kessler JA Nerve growth factor administration alters the expression of other neurotrophins in adult sensory ganglia. Soc Neurosci Abstr 1994; 20:1302.

33.

Gao WQ , Dybdal N. , Schmelzer C. , et al. Neurotrophin-3 reverses cisplatin induced peripheral neuropathy . Soc Neurosci Abstr 1994;20:442.

34.

Apfel SC , Arezzo JC , Lewis ME , Kessler JA The use of IGF-I in the prevention of vincristine neuropathy in mice . Ann NY Acad Sci 1993;692:243-245.

35.

Contreras PC , Steffler C. , Gruner JA , et al. Recombinant human insulin like growth factor—I (rhIGF-I) prevents cisplatin induced neuropathy. Soc Neurosci Abstr 1994;20:1096.

36.

Muller LJ , Gemtsen van der Hoop R. , Moorer-van Delft CM , Gispen WH , Roubos EW Morphological and electrophysiological study of the effects of cisplatin and org2766 on rat spinal ganglion neurons. Cancer Res 1990;50:2437-2442.

37.

Hamers FP , Pette C. , Neijt JP , Gispen WH The ACTH (4-9) analog, Org2766, prevents taxol induced neuropathy in rats . Eur J Pharmacol 1993;233:177-178.

38.

Kasayama S. , Oka T. Impaired production of nerve growth factor in the submandibular gland of diabetic mice. Am J Physiol 1989;257: E400-E404.

39.

Ordonez G. , Fernandez A. , Perez R. , Sotelo J. Low contents of nerve growth factor in serum and submaxillary gland of diabetic mice. J Neurol Sci 1994;121:163-166.

40.

Brewster WJ , Femyhough P. , Diemel LT , Mohiaddin L. , Tomlinson DR Diabetic neuropathy, nerve growth factor and other neurotrophic factors. Trends Neurosci 1994;17:321-325.

41.

Hellweg R. , Hartung HD Endogenous levels of nerve growth factor (NGF) are altered in expenmental diabetes mellitus: a possible role for NGF in the pathogenesis of diabetic neuropathy. J Neurosci Res 1990;26:258-267.

42.

Jakobsen J. , Bnmijoin S. , Skau K. , Sidenius P. , Wells D. Retrograde axonal transport of transmitter enzymes, fucose labelled protein and nerve growth factor in streptozocin-diabetic rats. Diabetes 1981;30:797-803.

43.

Calcutt NA , Muir D. , Powell HC , Mizisin AP Reduced ciliary neurotrophic factor like activity in nerves from diabetic or galactose fed rats. Brain Res 1992;575:320-324.

44.

Crosby SR , Tsigos C. , Anderton CD , et al. Elevated plasma insulin like growth factor binding protein-1 levels in type I (insulin dependent) diabetic patients with peripheral neuropathy . Diabetologia 1992;35:868-872.

45.

Apfel SC , Arezzo JC , Brownlee M. , Federoff H. , Kessler JA Nerve growth factor administration protects against expenmental diabetic sensory neuropathy. Brain Res 1994;634:7-12.

46.

Diemel LT , Brewster WJ , Femyhough P. , Tomlinson DR Expression of neuropeptides in experimental diabetes: effects of treatment with nerve growth factor or brain derived growth factor. Mol Brain Res 1994;21:171-175.

47.

Bravenboer B. , Kappelle AC , Van Buren T. , Erkelens DW , Gispen WH ACTH 4-9 analogue ORG 2766 can improve existing neuropathy in streptozocin induced diabetic rats. Acta Diabetol 1993;30:21-24.

48.

Bennett GJ , Xie YK A painful mononeuropathy in rat produces disorders of pain sensation like those seen in man. Pain 1988;33:87-107.

49.

Thomas D. , Ren K. , Dubner R. Nerve growth factor alleviates a painful peripheral neuropathy in rats. Soc Neurosci Abstr 1993;19:969.

50.

Oppenheim RW , Qin-Wei Y. , Prevetter D. , Yan Q. Brain derived neurotrophic factor rescues developing avian motoneurons from cell death. Nature 1992;360:755-757.

51.

Yan Q. , Elliott J. , Snider WD Brain derived neurotrophic factor rescues spinal motor neurons from axotomy induced cell death. Nature 1992;360:753-755.

52.

Sendtner M. , Kreutzberg GW , Thoenen H. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 1990 ;345:440-441.

53.

Arakawa Y. , Sendtner M. , Thoenen H. Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines . J Neurosci 1990;10:3507-3515.

54.

Sendtner M. , Schmalbruch H. , Stockll KA , et al. Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuropathy . Nature 1992;358:502-504.

55.

Gemtsen van der Hoop R. , Vecht CJ , Van der Burg Mel , et al. Prevention of cisplatin neurotoxicity with an ACTH (4-9) analogue in patients with ovarian cancer. N Engl J Med 1990;322:89-94.

56.

Lewis ME , Neff NT , Contreras PC , et al. Insulin like growth factor—I: potential for treatment of motor neuronal disorders. Exp Neurol 1993 ;124:73-88.

57.

Petty BG , Comblath DR , Adornato BT , et al. The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol 1994;36:244-246.

58.

Henderson JT , Semuk NA , Richardson PM , Gauldie J. , Roder JC Systemic administration of ciliary neurotrophic factor induces cachexia in rodents. J Clin Invest 1994;93:2632-2638.

59.

Lewin GR , Ritter AM , Mendell LM Nerve growth factor induced hyperalgesia in the neonatal and the adult rat . J Neurosci 1993;13:2136-2148.

60.

Schwartz JP , Breakfield XO Altered nerve growth factor in fibroblasts from patients with familial dysautonomia. Proc Natl Acad Sci U S A 1980;77:1154-1158.

61.

Breakfield XO , Orloff G. , Castiglione C. , Coussens L. , Axelrod FB , Ullrich A. Structural gene for beta-nerve growth factor not defective in familial dysautonomia. Proc Natl Acad Sci U S A 1984;81:4213-4216.

62.

Breakfield XO , Ozelius L. , Bothwell MA , et al. DNA polymorphisms for the nerve growth factor receptor gene exclude its role in familial dysautonomia . Mol Biol Med 1986;3:483-494.

63.

Edwards RH , Rutter WJ Use of vaccinia virus vectors to study protein processing in human disease. Normal nerve growth factor processing and secretion in cultured fibroblasts from patients with familial dysautonomia. J Clin Invest 1988; 82:44-47.

64.

Faradji V. , Sotelo J. Low serum levels of nerve growth factor in diabetic neuropathy. Acta Neurol Scand 1990;81:402-406.

65.

Amand P. , Rudge P. , Mathias CJ , et al. New autonomic and sensory neuropathy with loss of adrenergic sympathetic function and sensory neuropeptides. Lancet 1991;337:1253-1254.

66.

Takahashi R. , Yokoji H. , Misawa H. , et al. A null mutation in the human CNTF gene is not causally related to diseases. Nature Gen 1994;7:79-84.