The History of Nerve Growth Factor: From Molecule to Drug.

Nerve growth factor (NGF), the first neurotrophin to be discovered, has a long and eventful research journey with a series of turning points, setbacks, and achievements. Since the groundbreaking investigations led by Nobel Prize winner Rita Levi-Montalcini, advancements in the comprehension of NGF's functions have revolutionized the field of neuroscience, offering new insights and opportunities for therapeutic innovation. However, the clinical application of NGF has historically been hindered by challenges in determining appropriate dosing, administration strategies, and complications related to the production process. Recent advances in the production and scientific knowledge of recombinant NGF have enabled its clinical development, and in 2018, the United States Food and Drug Administration approved cenegermin-bkbj, a recombinant human NGF, for the treatment of all stages of neurotrophic keratitis. This review traces the evolutionary path that transformed NGF from a biological molecule into a novel therapy with potential research applications beyond the eye. Special emphasis is put on the studies that advanced NGF from discovery to the first medicinal product approved to treat a human disease.

Rita Levi and Nerve Growth Factor.

How to cite this article: Pai-Dhungat JV. Rita Levi and Nerve Growth Factor. J Assoc Physicians India 2023;71(9):106-106.

Great personalities of medicine, great lessons.

The analysis of three characters corresponding to different spaces and times shows the close link between literature and the history of medicine. On one hand, Don Quixote of La Mancha, who reflects the thought of the last years of the Renaissance and that has been assimilated in contemporary Mexico. On the other hand, Doctors Miguel Francisco Jiménez and Rita Levi Montalcini, who lived in the 19th and 20th centuries, respectively. Despite the years that separate these three personalities, many elements in common are observed that do not lose their validity: the value that is given to health, ethics, tenacity and experience to attain successful results. All three characters refer to the medicine of their time, their achievements and the promotion of humanism, always inherent to medicine.

El análisis de tres personajes correspondientes a espacios y tiempos diferentes muestra el estrecho vínculo entre la literatura y la historia de la medicina. Por un lado, don Quijote de la Mancha, quien refleja el pensamiento de los últimos años del Renacimiento y ha sido asimilado en el México contemporáneo. Por otro lado, los doctores Miguel Francisco Jiménez y Rita Levi Montalcini, quienes vivieron en los siglos XIX y XX, respectivamente. A pesar de los años que separan a los tres personaje, se advierten numerosos elementos en común que no pierden vigencia: el valor que se otorga a la salud, la ética, la tenacidad y la experiencia para obtener resultados exitosos, entre otros. Los tres personajes aluden a la medicina de su tiempo, los logros alcanzados y la promoción del humanismo, siempre inherente a la medicina.

Grandes personajes de la medicina, grandes lecciones / Great personalities of medicine. Great lessons

Resumen El análisis de tres personajes correspondientes a espacios y tiempos diferentes muestra el estrecho vínculo entre la literatura y la historia de la medicina. Por un lado, don Quijote de la Mancha, quien refleja el pensamiento de los últimos años del Renacimiento y ha sido asimilado en el México contemporáneo. Por otro lado, los doctores Miguel Francisco Jiménez y Rita Levi Montalcini, quienes vivieron en los siglos XIX y XX, respectivamente. A pesar de los años que separan a los tres personaje, se advierten numerosos elementos en común que no pierden vigencia: el valor que se otorga a la salud, la ética, la tenacidad y la experiencia para obtener resultados exitosos, entre otros. Los tres personajes aluden a la medicina de su tiempo, los logros alcanzados y la promoción del humanismo, siempre inherente a la medicina.

Abstract The analysis of three characters corresponding to different spaces and times shows the close link between literature and the history of medicine. On one hand, Don Quixote of La Mancha, who reflects the thought of the last years of the Renaissance and that has been assimilated in contemporary Mexico. On the other hand, Doctors Miguel Francisco Jiménez and Rita Levi Montalcini who lived in the 19th and 20th centuries, respectively. Despite the years that separate these three personalities, many elements in common are observed that do not lose their validity: the value that is given to health, ethics, tenacity and experience to attain successful results. All three characters refer to the medicine of their time, their achievements and the promotion of humanism, always inherent to medicine.

A new season for experimental neuroembryology: The mysterious history of Marian Lydia Shorey.

At the turn of the nineteenth and twentieth centuries, the landscape of emerging experimental embryology in the United States was dominated by the Canadian Frank Rattray Lillie, who combined his qualities as scientist and director with those of teacher at the University of Chicago. In the context of his research on chick development, he encouraged the young Marian Lydia Shorey to investigate the interactions between the central nervous system and the peripheral structures. The results were published in two papers which marked the beginning of a new branch of embryology, namely neuroembryology. These papers inspired ground-breaking enquiry by Viktor Hamburger which opened a new area of the research by Rita Levi-Montalcini, in turn leading to the discovery of the nerve growth factor, NGF.

The failed attribution of the Nobel Prize for Medicine or Physiology to Viktor Hamburger for the discovery of Nerve Growth Factor.

The announcement in October 1986 that the Nobel Prize for Physiology or Medicine was to awarded to Rita Levi Montalcini and Stanley Cohen for the discovery of nerve growth factor (NGF) and epidermal growth factor, respectively, caused many to wonder why Viktor Hamburger in whose laboratory the initial work was done had not been included in the award. This article try to reconstruct the history of the discovery of NGF with the aim to re-establish a correct dynamic of the events.

Looking at the future with Rita.

This paper on Rita Levi-Montalcini (1909-2012), who received in 1986 the Nobel Prize in Physiology or Medicine for the discovery of nerve growth factor, focuses on aspects of her advocacy and her commitment to education in which she has been especially active in the last part of her long life. With passionate confidence on the capabilities of the aging brain (together with severe admonition against the pursuit of immortality), she encouraged contributions of senior citizens to the society. Always projected into the future, with enduring faith in the potential of young individuals, in education as a key to development, in the capabilities of women, in the importance of gender equality, Rita established in 2001 the Rita Levi-Montalcini Foundation for the education of African women. Her legacy on engagement for a better 'global village' should not be forgotten by the neuroscience community.

Rita Levi-Montalcini and the discovery of NGF, the first nerve cell growth factor.

The nerve growth factor (NGF) is a signaling protein, discovered by Rita Levi-Montalcini in the early 1950's for its effect on growth and differentiation of specific populations of neurons of the peripheral nervous system. Originally identified as neurite outgrowth-stimulating factor, later studies revealed that the purified molecule has a number of target cells in the central nervous system and on nonneuronal cells. Moreover, recent studies showed the potential therapeutic properties of NGF in neuropathies of the central and peripheral nervous system and diseases of the eye and skin. Here I briefly describe the discovery of NGF, the early studies of Rita LeviMontalcini, a pioneer in modern neuroscience, and my scientific and human experience working in her laboratory for over 40 years.

The metabotrophic NGF and BDNF: an emerging concept.

The field of neurotrophins, particularly, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), has witnessed a number of breakthroughs in recent years. There is evidence now that NGF and BDNF mediate multiple biological phenomena, ranging from the Rita Levi Montalcini's neurotrophic through immunotrophic to epitheliotrophic and nociceptive effects. In 2003 we, for the first time, enriched the "NGFome" with one more expression presented in our concept of NGF metabotrophicity, also that of BDNF. This envisages that these two factors may operate as metabotrophins, that is, involved in the maintenance of cardiometabolic homeostasis (glucose and lipid metabolism as well as energy balance, cardioprotection, and wound healing). Recent results also demonstrated that the circulating and/or tissue levels of NGF and BDNF are altered in cardiometabolic diseases (atherosclerosis, obesity, type 2 diabetes, metabolic syndrome, and type 3 diabetes). Altogether, a hypothesis of metabotrophic deficit due to the reduction of NGF/BDNF availability and/or utilization was raised, and implicated in the pathogenesis of cardiometabolic diseases. This may cultivate a novel pathogenic and therapeutic thinking for these diseases.

Rita Levi-Montalcini: the discovery of nerve growth factor and modern neurobiology.

The remarkable accomplishments in developmental neurobiology within the past 60 years have depended on two things: (i) a succession of original histochemical and immunohistochemical methodologies for identifying pathways in the nervous system with increasing precision and sensitivity, and (ii) the discovery of growth factors for neurons. Growth factors are naturally occurring, essential biological mediators that promote cell growth, differentiation, survival and function in specific nerve cell populations. The discovery of nerve growth factor (NGF) by Rita Levi-Montalcini in the 1950s represents an important milestone in the processes that led to modern cell biology. NGF was the first growth factor identified, for its action on the morphological differentiation of neural-crest-derived nerve cells. Later, its effect on neuronal cells of the peripheral and central nervous systems, and on several non-neuronal cells was also determined. Thus, Levi-Montalcini's work on NGF represents, as acknowledged by the Nobel Prize Assembly in its press release of 13 October 1986, "a fascinating example of how a skilled observer can create a concept out of apparent chaos".